Activity of amlodipine against Staphylococcus aureus: association with oxacillin and mechanism of action.

Aim: This study was designed to evaluate the in vitro antimicrobial activity of amlodipine against Staphylococcus aureus strains. Materials & methods: The antimicrobial activity of amlodipine was evaluated by the broth microdilution method and its interaction with oxacillin was evaluated by checkerboard assay. The possible mechanism of action was evaluated by flow cytometry and molecular docking techniques. Results: Amlodipine showed activity against S. aureus between 64 and 128 µg/ml, in addition to showing synergism in approximately 58% of the strains used. Amlodipine also showed good activity against forming and mature biofilms. The possible mechanism of action may be attributed to its ability to lead to cell death. Conclusion: Amlodipine has antibacterial activity against S. aureus.

Antibacterial activity of paroxetine against Staphylococcus aureus and possible mechanisms of action.

Aim: To evaluate the antibacterial activity of paroxetine alone and associated with oxacillin against isolates of methicillin-sensitive and -resistant Staphylococcus aureus. Materials & methods: The broth microdilution and checkerboard techniques were used, with investigation of possible mechanisms of action through flow cytometry, fluorescence microscopy and molecular docking, in addition to scanning electron microscopy for morphological analysis. Results: Paroxetine showed a MIC of 64 µg/ml and bactericidal activity, mostly additive interactions in combination with oxacillin, evidence of action on genetic material and membrane, morphological changes in microbial cells and influence on virulence factors. Conclusion: Paroxetine has antibacterial potential from the perspective of drug repositioning.

Gallic acid leads to cell death of Candida albicans by the apoptosis mechanism.

Aim: To evaluate the antifungal activity of gallic acid (GA) against the strains of Candida spp. resistant to fluconazole and to determine its mechanism of action. Materials & methods: Antifungal activity was evaluated using the broth microdilution and flow cytometry techniques. Results: GA presented minimum inhibitory concentrations ranging from 16 to 72 µg/ml, causing alterations of the membrane integrity and mitochondrial transmembrane potential, production of reactive oxygen species and externalization of phosphatidylserine. Conclusion: GA has potential antifungal activity against Candida spp.

Antifungal activity of dexamethasone against fluconazole-resistant Candida albicans and its activity against biofilms.

Objective: The present study investigated the antifungal action of dexamethasone disodium phosphate (Dex). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol; M27-A3, checkerboard test and biofilm were evaluated with two isolates of Candida albicans, hyphal production test, molecular docking analysis and flow cytometry analysis. Result: Dex and fluconazole (FLC) together had a synergistic effect. Mature biofilm was reduced when treated with Dex alone or in combination. Dex and FLC promoted a decrease in the production of hyphae and changes in the level of mitochondrial depolarization, increased generation of reactive oxygen species, loss of membrane integrity, increased phosphatidylserine externalization and molecular docking; there was interaction with ALS3 and SAP5 targets. Conclusion: Dex showed antifungal activity against FLC-resistant C. albicans strains.

This study aimed to evaluate the antifungal action of dexamethasone against FLC-resistant C. albicans strains.

Synergistic activity of dobutamine combined with azoles and its mechanism of action against strains of Candida glabrata.

Aims: To evaluate the antifungal effect of dobutamine against Candida glabrata as well as its synergism with azoles and its action on biofilm. Methods: The M27-A3 protocol and flow cytometry were used for elucidation of the possible mechanism of action. Results: The tested isolates presented MICs ranging from 2 to 32 µg/ml for dobutamine, with fungistatic effect. A total of 82% of the strains showed synergism with fluconazole, with 90% showing synergism with itraconazole. The effect on biofilm formation was nonsignificant. Cytometry tests showed that dobutamine induced mitochondrial depolarization. Conclusion: Dobutamine has an antifungal effect on strains of C. glabrata and synergistic activity with azoles. This effect is probably mediated by increased oxidative damage to the membrane.

Activity of arginine-phenylalanine and arginine-tryptophan-based surfactants against Staphylococcus aureus.

Aims: This study aimed to evaluate the antibacterial effect of two new cationic surfactants based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM). Materials & methods: Antibacterial activity, mechanism of action and interactions with Staphylococcus aureus enzymes were measured through microbiological, flow cytometry and molecular docking assays, respectively. Results & conclusion: These compounds showed antibacterial activity in the range of 4.06-16.24 µg/ml against planktonic cells and no activity against mature biofilms, since they caused a loss of membrane integrity and increased DNA damage, as revealed by flow cytometry analysis. In silico assays revealed the existence of molecular bonds such as hydrogen bonds, mainly with DNA. Therefore, these compounds have promising pharmacological activity against MRSA strains.